Treatment-Resistant Depression in Real-World Clinical Practice: A Systematic Literature Review of Data from 2012 to 2022

Abstract

Objective: Real-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade.

Data sources: A literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022. Bibliographies of all relevant identified systematic reviews and relevant conference proceedings from 2020 to 2022 were manually hand-searched.

Study selection: Real-world studies, including cohort, cross-sectional, case-control, chart review and registry studies, published in English and reporting outcomes in adults with TRD, were included.

Data extraction: Extracted data included study and baseline disease characteristics, treatment type, treatment response, clinical outcomes and health-related quality of life.

Results: Twenty studies were included. Criteria for TRD varied, but patients typically experienced long-lasting depression (range 1.4 to 16.5 years). Across studies, mean disease severity scores demonstrated moderate to severe depression, reflecting a high burden of disease at baseline. Remission rates were typically low but generally increased with longer follow-up durations. However, the heterogeneity of interventions, follow-up durations (range 2 weeks to 9.4 years) and assessment tools precluded their quantitative synthesis. Studies were frequently limited by low sample size (range 14 to 411 patients) and health-related quality of life was infrequently assessed.

Conclusions: There is a lack of clinical consensus regarding the definition, assessment and monitoring of TRD in real-world practice. Nevertheless, TRD carries a high burden of illness and there is an unmet need for faster and more effective treatments. To better understand the personal burden of affected patients, future studies would benefit from standardisation of severity assessment and measures of treatment effectiveness, as well as greater consideration of health-related quality of life.

Keywords: Major depressive disorder; Real-world evidence; Systematic literature review; Treatment-resistant depression.

Fig. 1

Flowchart of studies included and excluded in the systematic review process. CDSR Cochrane Database of Systematic Reviews, CENTRAL Cochrane Central Register of Controlled Trials, MDD-PE major depressive disorder-psychiatric emergency, TRD treatment resistant depression, SLR systematic literature review

Fig. 2

Baseline depression severity scores. Data are presented as mean ± SD (where available). ^aGroup receiving antidepressant treatment. ^bGroup receiving second-generation antipsychotic plus antidepressant treatment. ^cPatients who subsequently experienced remission. ^dPatients who did not subsequently achieve remission. ^eSeverity classification for HAM-D score defined by Zimmerman et al. [41]. ^fSeverity classification for MADRS score defined by Muller et al. [42]. ^gSeverity classification for BDI score defined by Beck et al. [43]. ^hPatients who were THC-positive. ^IPatients who were THC-negative. ^jSeverity classification for PHQ-9 score defined by Kroenke et al. [44]. BDI Beck Depression Inventory, HAM-D Hamilton Depression Rating Scale, MADRS Montgomery–Åsberg Depression Rating Scale, PHQ-9 9-question Patient Health Questionnaire, SD standard deviation, THC Tetrahydrocannabinol

Fig. 3

Change in mean absolute depression severity scores over time. ^aGroup receiving antidepressant treatment. ^bGroup receiving second-generation antipsychotic plus antidepressant treatment. ^cSeverity classification for HAM-D score defined by Zimmerman et al. [41]. ^dRemission thresholds for HAM-D and MADRS previously defined by Zimmerman et al. [45]. ^eSeverity classification for MADRS score defined by Muller et al. [42]. ^fSeverity classification for BDI score defined by Beck et al. [43]. ^gRemission threshold for BDI previously defined by Riedel et al. [46]